Biochem - Metabolism (Fatty acid metabolism, Ketone bodies, & Metabolic fuel use)

Question 1

What does long-chain fatty acid degradation require?

Answer 1

Long-chain fatty acid degradation requires carnithine-dependent transport into mitochondrial matrix; Think:”CARNitine = CARnage of fatty acids”

Question 2

What is the major metabolic defect and effect in Carnitine deficiency?

Answer 2

Carnitine deficiency: inability to transport LCFAs into the mitochondria, resulting in toxic accumulation

Question 3

What are 3 symptoms/signs of Carnitine deficiency?

Answer 3

Causes weakness, hypotonia, and hypoketotic hypoglycemia

Question 4

What are 3 signs of Acetyl-CoA dehydrogenase deficiency?

Answer 4

High dicarboxylic acids, Low glucose and ketones

Question 5

What role does acetyl-CoA play in gluconeogenesis? What results from low acetyl-CoA?

Answer 5

Acetyl-CoA is a positive allosteric regulator of pyruvate carboxylase in gluconeogenesis; Low acetyl-CoA => Low fasting glucose

Question 6

What substance begins fatty acid synthesis?

Answer 6

Citrate; Think: “SYtrate = SYnthesis”

Question 7

Draw the major steps leading to fatty acid synthesis. Include the locations of the cell in which these occur.

Answer 7

See p. 115 in First Aid 2014 for visual in middle left of page

Question 8

Draw the major steps leading to fatty acid degradation. Include the locations of the cell in which these occur.

Answer 8

See p. 115 in First Aid 2014 for visual in middle right of page

Question 9

What is used to shuttle fatty acids to synthesis versus degradation? In what direction is each shuttle?

Answer 9

FATTY ACID SYNTHESIS: Citrate shuttle out of mitochondrial matrix into cytoplasm; FATTY ACID DEGRADATION: Carnitine shuttle out of cytoplasm into mitochondrial matrix

Question 10

Into what products does the liver metabolize fatty acids and amino acids, and why?

Answer 10

In the liver, fatty acids and amino acids are metabolized to acetoacetate and Beta-hydroxybutarate (to be used in muscle and brain)

Question 11

What are the 3 major conditions that lead to the production of ketone bodies, and what mechanisms/processes does this occur in each case?

Answer 11

In (1) prolonged starvation and (2) diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In (3) alcoholism, excess NADH shunts oxaloacetate to malate. Both processes cause a buildup of acetyl-CoA, which shunts glucose and FFA toward the production of ketone bodies

Question 12

How many kcal is each of the following: (1) 1 g protein or carbohydrate (2) 1 g fat (3) 1 g alcohol?

Answer 12

(1) 1 g protein or carbohydrate = 4 k cal (2) 1 g fat = 9 k cal (3) 1 g alcohol = 7 kcal

Question 13

Draw a graph of time (x - 2 sec, 10 sec, 1 min, & 2 hrs) versus % maximal energy by source, including the following graph lines: (1) Stored ATP (2) Creatine phosphate (3) Anaerobic metabolism (4) Aerobic metabolism (5) Overall performance.

Answer 13

See p. 116 in First Aid 2014 for visual at top of page.

Question 14

What are the body’s priorities in fasting and starvation states?

Answer 14

Priorities are to supply sufficient glucose to the brain and RBCs and to preserve protein

Question 15

What is considered to be the fed state? What fuel metabolism occurs in the fed state? What is the predominating mechanism?

Answer 15

Fed state (after a meal); Glycolysis and Aerobic respiration; Insulin stimulates storage of lipids, proteins, glycogen

Question 16

What is considered to be the fasting state? What fuel metabolism occurs in the fed state, and which is most minor vs. major? What is the predominating mechanism?

Answer 16

Fasting (between meals); Hepatic glycogenolysis (major); Hepatic gluconeogenesis, Adipose release of FFA (minor); Glucagon, adrenaline stimulate use of fuel reserves

Question 17

What are 4 processes that maintain blood glucose levels in days 1 to 3 of starvation?

Answer 17

Blood glucose levels maintained by: (1) Hepatic glycogenolysis (2) Adipose release of FFA (3) Muscle and liver, which shift fuel use from glucose to FFA (4) Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-CoA (from odd-chain FFA - the only triacylglycerol components that contribute to gluconeogenesis)

Question 18

When do glycogen stores deplete in starvation?

Answer 18

Glycogen reserves depleted after day 1

Question 19

What is important to know bout RBCs in the context of starvation?

Answer 19

RBCs lack mitochondria and so cannot use ketones

Question 20

Graph weeks of starvation (x) versus stored energy in kg (y), indicating the decline in the following energy sources: (1) Carbohydrate (2) Fat (3) Protein.

Answer 20

See p. 116 in First Aid 2014 for visual near middle/bottom right of page

Question 21

What is the main source of energy in starvation after day 3? What happens if this source is depleted?

Answer 21

Adipose stores (ketone bodies become the main source of energy for the brain). After these are depleted, vital protein degradation accelerates, leading to organ failure and death.

Question 22

What determines survival time in starvation after day 3?

Answer 22

Amount of excess stores determines survival time

Question 23

What is the main source of energy for the brain in starvation after day 3?

Answer 23

Adipose stores (ketone bodies become the main source of energy for the brain)